Bradley S G, Rose W C
Antimicrob Agents Chemother. 1973 Jun;3(6):686-92. doi: 10.1128/AAC.3.6.686.
Combinations of pactamycin and Salmonella typhosa 0901 endotoxin, administered simultaneously, killed more BALB/c mice than comparable doses of either agent alone The slopes of the dose-response curves for combinations of endotoxin and pactamycin were parallel to both that for endotoxin alone and the antitumor drug alone; therefore, no new mechanism of toxicity has been evoked by the combination. The synergistic toxicity of endotoxin and pactamycin was due to an in vivo interaction rather than a direct reaction between the two agents. Phenobarbital pretreatment protected the mice from toxicity of the antitumor agent alone but not from the lethal action of the combination. Pretreatment with endotoxin increased the resistance of the mice to both endotoxin alone and the combination. Third agents unable to protect mice from the synergistic toxicity of endotoxin and pactamycin were alpha[p-(fluoren-9-ylidenemethyl)-phenyl]-2-piperidine-ethanol, neomycin, phenylbutazone, polymyxin B, and tybamate. Prednisolone pretreatment alleviated the toxicity of the combination. For the restricted series of killed bacteria and bacterial products tested for capability to enhance the toxicity of pactamycin, only gram-negative bacterial cells were potent. These results indicated that pactamycin rendered the mice more susceptible to endotoxin and that endotoxin was the causal lethal agent.
将派来霉素与伤寒沙门氏菌0901内毒素同时给药，相比于单独使用同等剂量的任何一种药物，其杀死的BALB/c小鼠更多。内毒素与派来霉素联合用药的剂量反应曲线斜率，与单独使用内毒素和单独使用抗肿瘤药物的剂量反应曲线斜率平行；因此，联合用药并未引发新的毒性机制。内毒素与派来霉素的协同毒性是由于体内相互作用，而非两种药物之间的直接反应。苯巴比妥预处理可保护小鼠免受单独使用抗肿瘤药物的毒性，但不能保护其免受联合用药的致死作用。用内毒素预处理可增加小鼠对单独使用内毒素及联合用药的抵抗力。无法保护小鼠免受内毒素与派来霉素协同毒性的其他药物有α-[对-(芴-9-亚甲基)-苯基]-2-哌啶乙醇、新霉素、保泰松、多粘菌素B和泰巴氨酯。泼尼松龙预处理可减轻联合用药的毒性。在所测试的一系列用于增强派来霉素毒性的死菌和细菌产物中，只有革兰氏阴性菌细胞具有强效。这些结果表明，派来霉素使小鼠对内毒素更敏感，且内毒素是致死的致病因子。
